Ph 162A Lec 20: Viruses And Cancer

Front 1

[General Aspect of Cancer}

What is cancer?

Back 1

cancer = change in a cell that enables the cell to escape normal growth control mechanisms; that change is heritable from one cell to daughter cells, but not from one organism to the next generation

Front 2

The change (in cancer cells) usually involves a ______

Back 2

mutation = change in the gene structure or the addition of new genetic material

Front 3

maturation sequence

Back 3

steps a cell from a particular tissue takes to mature; have initial and final stage-- all tissues of the body differentiate according to a maturation sequence

Front 4

cells at its initial stage are called

Back 4

stem cell

e.g white blood cells

Front 5

cells at its final stage are called

Back 5

terminally differentiated cell

Front 6

Stem cell that is where you have the highest rate of ______ and little or no ______

Back 6

highest rate of cell division and little/no synthesis of hemoglobin or hemoglobin precursors

Front 7

What is terminal differentiation? (what happen at this stage?)

Back 7

note: there is greater division at the beginning of the sequence. At each division one daughter cell remains the same; and the other becomes more mature.

**At the end of the of the sequence cells do not divide and are programmed to die after a certain amount of time

Front 8

cells will usually change their ______ as they go through this maturation process

Back 8

morphology

Front 9

what is the purpose of maturation sequence?

Back 9

allows for the proliferation of cells:

1. development -- from the embryo to an individual, all the way to adulthood
2. tissue renewal -- after injury
3. development of adult tissues for special sporadic functions -- this happens as the organisms develops into adult (e.g for female reproduction, you have the uterus and breast)

Front 10

________ keeps the cell number constant. ________ eliminates the same number of cells as have arisen anew, and keeps normal tissues from overgrowing the host.

Back 10

1. terminal differentiation
2. programmed cellular death

note: these twos help control the total cell number

Front 11

cells become transformed into cancer cells only at ______

Back 11

earlier steps of maturation (early stages)

Front 12

Why does cells transformed into cancer cells only at early stages? and what is the cellular basis of how cancer works.

Back 12

Because DNA synthesis is required for the transformational event

note: therefore only the immature cells that are dividing are the ones that become transformed and this is why cancers of the muscle and the nerves occur very young children but not adults

Front 13

What is the cellular basis of how cancer works?

Back 13

when normal cell becomes genetically altered to a cancer cell, its progression through the maturation sequence becomes blocked, and it does not terminally differentiate and die. Instead it continues to divide and its daughter cells accumulate to form a tumor.

Front 14

How do we define cancer?

Back 14

The best way to define cancer is as a family of different diseases.

--they have different organs, they have diff causes, the treatment will be different from cancer to cancer, and survival of the patient will be different from cancer to cancer.

Front 15

Despite all the differences of cancers, they all involve some type of _________ event of an immature cell and this blocks normal cell differentiation.

Back 15

transformation

Front 16

[defining terms that are use to describe cancers]

tumor

Back 16

any bulge or swelling; usually means that due to cellular growth

Front 17

neoplasm

Back 17

new (abnormal) cellular growth (beyond the normal amount)

Front 18

benign

Back 18

having some abnormal growth but not spreading to distant sites via lymph or blood

Front 19

malignant

Back 19

having abnormal growth and potential for spreading to distant sites via lymph or blood

Front 20

metastasize

Back 20

to spread to distant sites via blood or lymph

Front 21

cancer

Back 21

malignant tumor; 3 types having different names depending on the tissues involved.

Front 22

name the three basic types of cancer:

Back 22

1. carcinoma
2. sarcoma
3. leukemias and lymphoma

Front 23

1. carcinoma (CA)

Back 23

involves epithelial cells; skin, linings of glands, organs, body cavities: breast, lung, colon, prostate cancer are carinomas

Front 24

2. sarcoma

Back 24

involves connective tissue e.g bone, muscle

Front 25

3. leukemias and lymphoma

Back 25

involve blood cells

Front 26

[What causes Cancer]

What causes cancer?

Back 26

the cause is the initiation of the first event that causes the cellular genetic change

Front 27

cancer-causing agents are called ______

Back 27

carcinogens

Front 28

the process of of causing cancer is

Back 28

carcinogenesis (oncogenesis)

Front 29

Carcinogens fall into 3 categories:

Back 29

1. chemical carcinogens
2. radiation
3. viruses

Front 30

1. chemical carcinogens

Back 30

cigarette smoke has a component to which is known to cause cancer

Front 31

2. radiation

Back 31

due to medical X-rays, working with radioactive isotopes from a medical or industrial exposure, UV light, and/or natural cosmic radiation in the environment

Front 32

3. viruses (the most important one that we are going to learn)

Back 32

the types of cancers they cause are all infectious diseases b/c a host-parasite relationship is involved.

Front 33

viruses that cause cancer all called

Back 33

oncogenic viruses

Front 34

[Oncogenic Viruses]

In order to cause cancer, a virus must have several properties. Name two that they must have:

Back 34

1. it must be lysogenic; not lytic
2. it must be able to alter the cell's growth pattern

note: lysogenic = it can persist w/in the infected cells, associate itself with the host genome, and persist from one generation to the next generation and at some point, it causes the genetic change.
**lytic = virus kills the cell, and so the cells cannot survive to divide and form a tumor

Front 35

The mechanism for all viruses that cause human cancers is through a ________

Back 35

transforming gene

Front 36

what is a transforming gene?

Back 36

a viral gene that codes for a cancer-causing protein.

Front 37

how does altering cell growth through the transforming gene effect transformation?

Back 37

the transforming protein of each different human cancer virus interacts with its own specific set of cellular molecules to effect transformation

Front 38

What 3 types of inspections are performed by camp maintenance?

Back 38

Controlled inspections
Operator Inspections
annual inspections

Front 39

[cervical cancer]

cancer of the

Back 39

uterine cervix
**the cervix is the neck of the uterus that extends into the vagina

Front 40

[cervical cancer]

etiology

Back 40

human papillomavirus **type 16 and 18

Front 41

[Cerivical cancer: Epidemiology]

incidence: It makes up about ____ percent of all cancers in the U.S. About _____ death per year. In ________ countries, 25% of all cancers are cervical cancers. This is the highest incidence of any cancer.

Back 41

1. 1%
2. 5000 deaths per year
3. Latin American countries

Front 42

[Cervical cancer]

1. Reservoir
2. Transmission

Back 42

1. humans
2. sexually transmitted

notes: the earlier the age of intercourse, the more likely the women are of developing cervical cancer-- it has to do with hormonal balances in a teenager rendering the cervical cells more

Front 43

[Cervical cancer]

Pathology
--where does the virus infects?
--how does it infects?

Back 43

**This is a carcinoma, so the virus infects squamous epithelial cells of the cervix.
**this virus has two transforming genes--these genes produce a product that will bind and inactivate tumor suppressor proteins

Front 44

[Cervical cancer]

Clinical manifestations
--signs and symptoms
--hints: there are 3 levels of severity

Back 44

note: fits the iceberg concept-- the infection of the female genital tract w/ the ocogenic types will have different gradations of severity:

Subclinical
**1st level: women have evidence of infection by the oncogenic HPV types but haven't developed or have any detectable signs of disease.

**2nd level: cervical dysplasia-- pre-cancerous stage; occurs about 2-10 years after the initial infection, yet there are no symptoms that are detectable by the woman

Clinical (more severe):
**3rd level-- cervical carcinoma (occurs 10-30 years after initial infection) at this point the patient will have signs and symptoms in advanced stages.
--the main signs is: bleeding b/w menstrual periods, bleeding after intercourse, and bleeding after menopause.
--Pain only develops very late when the cancer has begum to spread to other organs

Front 45

[Cervical cancer]

________ is thought to be a cofactor in cervical cancer.

Back 45

Tobacco
**risk of cervical cancer is much higher in smokers

Front 46

[Cervical cancer]

Diagnosis:

Back 46

**appearance of the cervix
**Papanicolaou smear or Pap smear--> the cervix is swabbed, and the cells are stained; the abnormal cells are identified base on morphology-- **large nucleated cells (immature cells that are beginning to replicate and this is during cervical dysplasia)
**Carcinoma is where you have severe growth and you'll see a cluster of large nucleated cells.

Front 47

[Cervical cancer]

Treament

Back 47

note: treatment is dependent upon the stage of the disease.

**for cervical dysplasia-- these cancerous cell can be removed by a process called CONIZATION = a surgical procedure where the tissue around the cervical opening is removed

**in the cased of cervical cancer-- It must be eliminated by a HYSTERECTOMY = removal of the uterus

important note: as long as the cancer has not metastasized, this cancer is completely curable w/ a hysterectomy

Front 48

[Cervical cancer]

Prevention

Back 48

1. Primary prevention-- same strategies used to prevent STD
--health education

2. Secondary prevention: annual Pap smears-- recommended for women who are sexually active or at least over the age of 20

Front 49

[Buckitt's lymphoma and nasopharyngeal carcinoma]

etiology

Back 49

Epstein-Barr virus (EBV)

--a DNA virus that is a member of the herpes family. It is the same virus that causes infectious mononucleosis.

Front 50

[Buckitt's lymphoma and nasopharyngeal carcinoma]

1. reservoir
2. transmission

Back 50

1. humans
2. close oral-oral contact

Front 51

[Buckitt's lymphoma and nasopharyngeal carcinoma]

Pathogenesis:

Back 51

A certain of these viruses will infect B lymphocytes and remain lysogenic. In a small percentage of infections, B lymphocyte can transform into a cancer cell.

Front 52

[Buckitt's lymphoma and nasopharyngeal carcinoma]

clinical manifestations: early stage

Back 52

note: follow the iceberg concept

**most people who are infected with EBV develop no symptoms but produce antibodies.
----> most infected people are asymptomatic but some of their lymphocytes may be transformed by EBV ---> (what caused these transformed?) these transformed cell lines can be derived from healthy blood donors

Front 53

[Buckitt's lymphoma and nasopharyngeal carcinoma]

clinical manifestations:

Then you have a more severe form, people that develop symptoms. What are these symptoms?

Back 53

develop symptoms as infectious mononucleosis

Front 54

[Buckitt's lymphoma and nasopharyngeal carcinoma]

clinical manifestations:

And the most serious manifestations of EBV is ____

Back 54

cancer

Front 55

[Buckitt's lymphoma and nasopharyngeal carcinoma]

clinical manifestations:

There are two possible forms of EBV cancers. They are?

Back 55

1. Burkitt's lymphoma
2. nasopharyngeal carcinoma

Front 56

[Buckitt's lymphoma and nasopharyngeal carcinoma]

What is Burkitt's lymphoma?

Back 56

very large tumors made of malignant lymphocytes and usually originating in the jaw; found primarily in African children

Front 57

[Buckitt's lymphoma and nasopharyngeal carcinoma]

What is Nasopharyngeal carcinoma (NPC)?

Back 57

tumors arise in lymphoid tissue of the nasopharynx and metastasize early to lymph nodes in the neck; occurs primarily in Asians-- particularly southern Chinese, and certain black populations in Africa and Native Americans in the Arctic region

Front 58

[Buckitt's lymphoma and nasopharyngeal carcinoma]

clinical manifestations:

Why do they have different manifestations if the etiologic agent is the same?

Back 58

**there must be some kind of cofactor that present along with the Epstein-Barr virus in order for the malignant disease to occur.

--for Burkitt's lymphoma, the best cofactor proposed seems to be malaria-- the geographic distribution of Burkitt's lymphoma is very similar to that of malaria
--for nasopharyngeal carcinoma, the cofactor is thought to be either a chemical carcinogen or possibly a strong genetic predisposition among Asian populations. It is thought that the use of snuff and incense has been implicated as a chemical co-carcinogen.

Front 59

[Buckitt's lymphoma and nasopharyngeal carcinoma]

Diagnosis

Back 59

**biopsy of the tumor **identification by pathologist-- of what is characteristic of the immature cells (looking for immature cells)
**There is an early diagnostic test for nasopharyngeal carcinoma. It is elevated IgA to the Epstein-Barr virus.

Front 60

[Buckitt's lymphoma and nasopharyngeal carcinoma]

Treatment

Back 60

**Burkitt's lymphoma-- is by chemotherapy with chemicals that will kill the rapidly dividing cells.

**nasopharyngeal carcinoma-- most of the cases are incurable because by the time it is detected, it means that it has already metastasized. The first symptoms are usually a swollen lymph node in the neck, which represents this metastasis. You can use radiation to slow the growth, but mainly, it is just to palliate.

Front 61

[Buckitt's lymphoma and nasopharyngeal carcinoma]

Prevention

Back 61

There is no prevention-- except possibly to remove these cofactors. This includes preventing malaria, or in the case of nasopharyngeal carcinoma, limiting or removing chemical carcinogens

Front 62

[Primary Hepatocellular Carcinoma (HPC)]

etiology

Back 62

HPC = is liver cancer

**cause by the hepatitis B virus

Front 63

[Primary Hepatocellular Carcinoma (HPC)]

1. Reservoir
2. transmission

Back 63

1. humans
2. transmission is by the blood-borne route

note: same as serum hepatitis

Front 64

[Primary Hepatocellular Carcinoma (HPC)]

Incidence: The areas that has the highest incidence of _____ also has the highest incidence of hepatocellular carcinoma (HPC)

Back 64

serum hepatitis

Front 65

[Primary Hepatocellular Carcinoma (HPC)]

Pathology

Back 65

**infects the liver cells
--establish a long-term infection --> virus often integrated into the host cell DNA--> the transforming gene of the virus codes for a protein that inhibits DNA repair--> as the DNA of the cells is being constantly injured, it can no longer repair itself--> it accumulates a series of mutations---> and with the right combination of mutations occurs the cells will become cancerous

Front 66

[Primary Hepatocellular Carcinoma (HPC)]

Clinical manifestations

Back 66

note: HPC is the tip of an iceberg

**most infections are asymptomatic
**some infected persons develop hepatitis
**a very small percent of infected persons develop HPC; individuals exposed to HBV (hepatitis B virus) during pregnancy or at birth are at highest risk

Front 67

[Primary Hepatocellular Carcinoma (HPC)]

Diagnosis

Back 67

**Early diagnosis can be made by the detection of a compound known as alpha-fetoprotein

Front 68

what is alpha-fetoprotein?

Back 68

a protein produced by immature liver cells at the beginning of the cell maturation sequence

Front 69

[Primary Hepatocellular Carcinoma (HPC)]

Prevention

Back 69

note: similar to hepatitis B

**vaccine
**and people with positive HBV should get regularly monitor of alpha-fetoprotein after age 40

Front 70

[Adult T-cell leukemia and lymphoma]

etiology

Back 70

caused by human T-cell leukemia virus

**this is an RNA virus and a retrovirus---so it has its own reverse transcriptase enzyme. This enables them to make a DNA copy of their RNA genome. And then, this DNA copy is inserted into the host cell genome as a lysogenic virus.

Front 71

[Adult T-cell leukemia and lymphoma]

1. reservoir
2. transmission

Back 71

1. humans
2. blood-borne route, sexually transmitted through body fluids, milk, and breastfeeding (most common method of transmission in endemic areas)

Front 72

[adult T-cell leukemia and lymphoma]

incidence

Back 72

rare in USA but more common in Japan, the Caribbean and parts of Africa

Front 73

[adult T-cell leukemia and lymphoma]

Pathology

Back 73

virus infects the T lymphocytes that have the CD4 marker. (That is the same cell type and the same marker that HIV infects.) And it works in a similar fashion. The transforming gene (similar to that of the hepatitis B virus) has a transforming protein that inhibits DNA repair.

Front 74

[adult T-cell leukemia and lymphoma]

Clinical Manifestations

Back 74

signs and symptoms are typical of leukemia-- this includes fatigue, anemia, and a tendency to bleed

Front 75

[adult T-cell leukemia and lymphoma]

Diagnosis

Back 75

*detect for serum antibodies against the virus, as well as finding the characteristics leukemic cells in the bloodstream-- will see immature white blood cells accumulate in the blood

Front 76

[adult T-cell leukemia and lymphoma]

Treatment

Back 76

treatment is through chemotherapeutic drugs-- targeting rapidly growing cells

Front 77

[adult T-cell leukemia and lymphoma]

Prevention

Back 77

preventative measures include the usual ones we have talked about for blood-borne disease--- screening of donated blood, preventive measures for STD

**in endemic areas, methods include testing pregnant women if found positive, warn them not to breastfeed or pasteurize their breast milk